The long range goal of this work is to obtain a better understanding of the molecular mechanisms involved in cell mediated immunity. Our major emphasis continues to be on the characterization of the natural cytotoxicity exhibited by normal human peripheral blood lymphocytes for cultured cell lines. We have developed an assay system which employs the principles of enzyme kinetics for the quantitative determination of the kinetic parameters of natural cytotoxicity, including the kinetic parameters for inhibition experiments. Using this assay system, we have established that cultured human cell lines exhibit a multiplicity of antigens recognizable by natural killer cells, and that some of these antigens are shared by different cell lines. Our data also support the clonal nature of natural killer cells, with each clone recognizing one antigen on one or more cell lines. We have been able to solubilize antigens from some target cells and have shown that they can inhibit natural killing. We now intend to attempt the large scale purification and characterization of some of these antigens. Further, we continue to investigate the relationship between natural and antibody dependent cytotoxicity effector mechanisms, and the enhancement of these lytic systems by interferon, culture with mitogens or with allogeneic cells.